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Our study examined how different titanium alloy Ti6Al4V (Ti64) and zirconia (ZrO2) surfaces, ranging from rough to very smooth, affect the expression of elastase (NE), matrix metalloproteinase (MMP)-8, MMP-9, and extracellular traps (NETs) by neutrophils. Discs of Ti64 and ZrO2, 10 mm in diameter and 1.5 mm thick, were created using diamond-impregnated polishing burs and paste to produce rough (Ra > 3 µm), smooth (Ra ≥ 1 to 1.5 µm), and very smooth (Ra < 0.1 µm) surfaces. Neutrophils from Wistar rats were cultured on these surfaces, and the culture supernatants were then examined for NE, MMP-8, and MMP-9 using ELISA. At the same time, NET formation was demonstrated immunohistochemically by staining neutrophils with CD16b and DNA with DAPI. Overall, the expressions of NE and MMP-8 were significantly higher from neutrophil culture on Ti64 and ZrO2 rough surfaces compared to the very smooth surface (R > S > VS) after 2 h and 4 h of culture. The expression of MMP-9 also increased with culture time; however, no significant surface effects on expression were observed. Similarly, rough Ti64 and ZrO2 surfaces (R & S) also showed significantly larger NET formation compared to the very smooth surface (VS) after 4 h and 8 h cultures. Our findings suggest that increasing surface roughness on Ti64 and ZrO2 triggers higher NE, MMP-8, and NET formation secretion.

Background and purpose: In recent years, sedentary behaviour (SB) has become a significant risk factor for health, alongside the decline of physical activity (PA) in the population. This study explored adolescents’ PA and SB using a longitudinal design, from the age of 13 to 15, to elucidate any changes and when they potentially occur. Method: The data material from the accelerometer measurements was analysed using the program SPSS, version 28. Repeated measures ANOVA (and follow-up test with Bonferroni corrections) were used to assess changes in the four activity levels during the three years. Independent t-tests were used to examine gender differences in each year and at each activity level and to determine differences in activity level between participants with valid data for all three years and those with valid data only at 13 and/or 14 years of age. Results: Statistical analyses of the accelerometer measurements revealed a significant increase in time in the lowest activity level and a decrease in light, moderate and vigorous intensity PA levels during the three years. These changes were larger from 13 to 14, than from 14 to 15, years of age. However, no significant interaction was found between time and gender. Analyses also showed a significantly higher time spent in SB and lower time spent in moderate activity among girls compared to boys at 13, but not at the age of 14 and 15. Conclusions: The findings, which indicate a reduction in PA and increased sedentary time with increasing age, are discussed, which we argue are important to increase and solidify involvement in PA among adolescents. Emphasized here is the importance of communicating the diverse possibilities of movement and challenging understandings of what PA can be for youth.

The prevalence of multiple age-related cardiovascular disease (CVD) risk factors is high among individuals living in low- and middle-income countries. We described receipt of healthcare services for and management of hypertension and diabetes among individuals living with these conditions using individual-level data from 55 nationally representative population-based surveys (2009-2019) with measured blood pressure (BP) and diabetes biomarker. We restricted our analysis to non-pregnant individuals aged 40-69 years and defined three mutually exclusive groups (i.e., hypertension only, diabetes only, and both hypertension-diabetes) to compare individuals living with concurrent hypertension and diabetes to individuals with each condition separately. We included 90,086 individuals who lived with hypertension only, 11,975 with diabetes only, and 16,228 with hypertension-diabetes. We estimated the percentage of individuals who were aware of their diagnosis, used pharmacological therapy, or achieved appropriate hypertension and diabetes management. A greater percentage of individuals with hypertension-diabetes were fully diagnosed (64.1% [95% CI: 61.8-66.4]) than those with hypertension only (47.4% [45.3-49.6]) or diabetes only (46.7% [44.1-49.2]). Among the hypertension-diabetes group, pharmacological treatment was higher for individual conditions (38.3% [95% CI: 34.8-41.8] using antihypertensive and 42.3% [95% CI: 39.4-45.2] using glucose-lowering medications) than for both conditions jointly (24.6% [95% CI: 22.1-27.2]).The percentage of individuals achieving appropriate management was highest in the hypertension group (17.6% [16.4-18.8]), followed by diabetes (13.3% [10.7-15.8]) and hypertension-diabetes (6.6% [5.4-7.8]) groups. Although health systems in LMICs are reaching a larger share of individuals living with both hypertension and diabetes than those living with just one of these conditions, only seven percent achieved both BP and blood glucose treatment targets. Implementation of cost-effective population-level interventions that shift clinical care paradigm from disease-specific to comprehensive CVD care are urgently needed for all three groups, especially for those with multiple CVD risk factors.

Contemporary post-industrial riverside areas like Marvila and Beato, in Lisbon, are being addressed by public and private bodies towards their urban regeneration. The aim of this paper is to present the ROCK project analysis of cultural heritage meaning, reappropriation and urban sustainability. Methodologically, we developed an inquiry to the local population around the residents’ perceptions on cultural heritage, the ongoing changes and existing retail, a cultural heritage mapping, and a conceptual analysis on urban sustainability. The results show the residents’ vision on cultural heritage and its relationship with the social and spatial changes, and the resilience process strengthening urban decayed areas, as a crucial element for urban life and socioeconomic development. Our conclusions present the relevance of cultural heritage as a public and private investment against the urban crisis, as well as the diversity in the process of cultural heritage reappropriation, including the residents’ participation to cultural led commodification processes developed by private companies.

Reliability in the electrical drives is becoming an important issue in many applications. In this context, the reliability associated to the switched reluctance machine (SRM) is also an important area of research. One of the major problems, that strongly affect its operation, are drive power semiconductors faults. Typical power converter topologies used in SRM drives cannot handle faults in their power semiconductors. So, this paper presents a power converter topology that provides fault-tolerant capabilities to the drive under a switch fault. This power converter will be used considering that a change in the direction of the current that flows in the SRM windings does not affect the behavior of the machine. Besides that, the proposed power converter will allow to generate multilevel phase voltages in order to apply different voltage levels as function of the SRM speed. A laboratory power converter was developed to test the SRM drive in normal and faulty conditions. From the obtained results it was possible to verify the fault-tolerant capability of the drive under switch faults in different devices and failure modes. It was also possible to confirm the multilevel operation of the drive.

Summary: Background: Given the increasing prevalence of diabetes in low-income and middle-income countries (LMICs), we aimed to estimate the health and cost implications of achieving different targets for diagnosis, treatment, and control of diabetes and its associated cardiovascular risk factors among LMICs. Methods: We constructed a microsimulation model to estimate disability-adjusted life-years (DALYs) lost and health-care costs of diagnosis, treatment, and control of blood pressure, dyslipidaemia, and glycaemia among people with diabetes in LMICs. We used individual participant data—specifically from the subset of people who were defined as having any type of diabetes by WHO standards—from nationally representative, cross-sectional surveys (2006–18) spanning 15 world regions to estimate the baseline 10-year risk of atherosclerotic cardiovascular disease (defined as fatal and non-fatal myocardial infarction and stroke), heart failure (ejection fraction of

Objectives To examine whether the gender of applicants and peer reviewers and other factors influence peer review of grant proposals submitted to a national funding agency.Setting Swiss National Science Foundation (SNSF).Design Cross-sectional analysis of peer review reports submitted from 2009 to 2016 using linear mixed effects regression models adjusted for research topic, applicant’s age, nationality, affiliation and calendar period.Participants External peer reviewers.Primary outcome measure Overall score on a scale from 1 (worst) to 6 (best).Results Analyses included 38 250 reports on 12 294 grant applications from medicine, architecture, biology, chemistry, economics, engineering, geology, history, linguistics, mathematics, physics, psychology and sociology submitted by 26 829 unique peer reviewers. In univariable analysis, male applicants received more favourable evaluation scores than female applicants (+0.18 points; 95% CI 0.14 to 0.23), and male reviewers awarded higher scores than female reviewers (+0.11; 95% CI 0.08 to 0.15). Applicant-nominated reviewers awarded higher scores than reviewers nominated by the SNSF (+0.53; 95% CI 0.50 to 0.56), and reviewers from outside of Switzerland more favourable scores than reviewers affiliated with Swiss institutions (+0.53; 95% CI 0.49 to 0.56). In multivariable analysis, differences between male and female applicants were attenuated (+0.08; 95% CI 0.04 to 0.13) whereas results changed little for source of nomination and affiliation of reviewers. The gender difference increased after September 2011, when new evaluation forms were introduced (p=0.033 from test of interaction).Conclusions Peer review of grant applications at SNSF might be prone to biases stemming from different applicant and reviewer characteristics. The SNSF abandoned the nomination of peer reviewers by applicants. The new form introduced in 2011 may inadvertently have given more emphasis to the applicant’s track record. We encourage other funders to conduct similar studies, in order to improve the evidence base for rational and fair research funding.

Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

Our study examined how different titanium alloy Ti6Al4V (Ti64) and zirconia (ZrO2) surfaces, ranging from rough to very smooth, affect the expression of elastase (NE), matrix metalloproteinase (MMP)-8, MMP-9, and extracellular traps (NETs) by neutrophils. Discs of Ti64 and ZrO2, 10 mm in diameter and 1.5 mm thick, were created using diamond-impregnated polishing burs and paste to produce rough (Ra > 3 µm), smooth (Ra ≥ 1 to 1.5 µm), and very smooth (Ra < 0.1 µm) surfaces. Neutrophils from Wistar rats were cultured on these surfaces, and the culture supernatants were then examined for NE, MMP-8, and MMP-9 using ELISA. At the same time, NET formation was demonstrated immunohistochemically by staining neutrophils with CD16b and DNA with DAPI. Overall, the expressions of NE and MMP-8 were significantly higher from neutrophil culture on Ti64 and ZrO2 rough surfaces compared to the very smooth surface (R > S > VS) after 2 h and 4 h of culture. The expression of MMP-9 also increased with culture time; however, no significant surface effects on expression were observed. Similarly, rough Ti64 and ZrO2 surfaces (R & S) also showed significantly larger NET formation compared to the very smooth surface (VS) after 4 h and 8 h cultures. Our findings suggest that increasing surface roughness on Ti64 and ZrO2 triggers higher NE, MMP-8, and NET formation secretion. [ABSTRACT FROM AUTHOR]

The enhancement of cultural heritage for tourism can greatly benefit from the opportunities offered by Information and Communication Technologies (ICTs), promoting greater interaction and integration between all stakeholders and service providers. In recent years, ICT applications and platforms have tended to provide a platform to translate the strategic goals and performance metrics of cultural heritage tourism into comprehensive services tailored to stakeholders’ needs by participating stakeholders. A successful co-designed platform integrates explicit services—requiring specialized software tools—and implicit services, facilitating evaluation processes. This adaptability ensures continuous improvement and alignment with evolving strategies and business objectives. As part of the European project, the development of the TExTOUR open ICT platform marks a significant advancement in leveraging technology within cultural tourism. It exemplifies the creation of a sustainable and adaptable framework, co-designed specifically to support and amplify the strategic objectives of cultural heritage tourism. This approach not only fosters better engagement and management within the sector but also sets a new standard for innovation in cultural tourism practices.

Abstract Objective Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/− mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/− mice have altered seizure susceptibility at light and dark phases. Methods We assessed seizure susceptibility and progression in a Tsc2+/− mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non‐active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. Results We found increased seizure susceptibility in Tsc2+/− mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/− males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/− females were more susceptible during the dark and post‐ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. Significance The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC‐related epilepsy research. Plain Language Summary Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

Immunotherapy has paved the way for the development of solid tumor new treatments in the last decade. The approval of immune checkpoint inhibitors such as anti PD-1/PD-L1 provided a revolution with optimal results. However, a considerable proportion of patients experience adverse therapeutic effects, and up to 50% may develop secondary resistance in the first three to five years. This has prompted the need for identifying new targets for immunotherapy that have good tolerance and biosafety and, of course, good tumoral response, either alone or in combination. Two of these new targets are the Lymphocyte-activation gene 3 (LAG-3) and the T cell immunoglobulin and ITIM domain (TIGIT). They are responsible for several interactions with the immune system, prompting an immunosuppressive phenotype in the tumor microenvironment. Both LAG-3 and TIGIT can be druggable, alone or in combination with anti-PD-1/PD-L1, with rather safe profiles making them attractive. In this review, we highlight some of the immune mechanisms of TIGIT and LAG-3 and their detection by immunohistochemistry, providing some insight into their use in the clinical setting.